Clinical Pharmacokinetics

Question 1

What is F for IV administration?

Answer 1

100%

Question 2

How does ionization affect distribution?

Answer 2

nonionized forms are more readily distributed

Question 3

Why are tube feeds important factors for oral/enteral administration?

Answer 3

• where does the tube feed end
• will the drug be absorbed in that location
• will the drug be able to travel through a tube feed

Question 4

Why shouldn’t you crush sustained release drugs?

Answer 4

makes it more bioavailable

Question 5

Describe the impact of thick vs. thin skin on topical absorption.

Answer 5

thicker skin is less absorptive because it has more layers

thinner skin may be too absorptive and can increase concentration levels

Question 6

How does perfusion rate affect distribution?

Answer 6

lower perfusion rate limits exposure to drug

• decreased absorption/distribution
• must increase dose

Question 7

How does protein binding affect Vd?

Answer 7

• high binding = low Vd

- low binding (more free) = high Vd

Question 8

How does BBB affect pharmacokinetics?

Answer 8

• if meninges are inflamed, spaces are increased and there is better distribution of the drug
• if meninges are noninflamed, spaces are tighter and there is minimal penetration of the BBB
• low protein binding drugs cross the BBB more easily

Question 9

Define Phase I and Phase II hepatic metabolism.

Answer 9

Phase I - redox, hydrolysis via cytochrome P450 enzymes

Phase II - conjugation (acetylation, sulfation, glucuronidation)

Question 10

How does CrCL change with age?

Answer 10

renal function decreases with age

Question 11

How does hemodialysis affect pharmacokinetics?

Answer 11

may filter out small, hydrophilic drugs

Question 12

How do neonates vary from population pharmacokinetics?

Answer 12

• thinner skin, more absorption of topical administration
• increased ECF (puffy) => increased absorption of hydrophilic drugs
• immature kidneys => decreased elimination

Question 13

How do elderly patients vary from population pharmacokinetics?

Answer 13

• thinner skin, more absorption of topical administration
• increased adipose => increased absorption of fat-soluble drugs
• decreased ECF => decreased Vd
• renal function decreases with age

Question 14

What is steady state dependent on?

Answer 14

half-life

Question 15

Why is steady state important?

Answer 15

• prevents over and under-dosage

- assumes maximum and stable dosage

Question 16

List types of drug interactions.

Answer 16

drug-drug
drug-nutrient
drug-disease
level of drug

Question 17

List causes of drug interactions.

Answer 17

drug incompatibility
- precipitation with Ca or NaCl
absorption
- chelation 
- stomach pH
distribution
- competition for binding sites
- changes in protein binding for disease states
- changes in ECF or adipose
metabolism
- inducer of CYP450 increases hepatic metabolism
- inhibitor of CYP450 decreases hepatic metabolism
elimination
- renal is most common
- competition
pharmacodynamics
- food interactions
- disease states
- some meds prolong QT intervals
- immunosuppressants
- some meds increase BG (steroids)